Excessive cutaneous scarring is an area of unmet medical need and causes functional, cosmetic and psychological morbidity. See. e.g., Hunt, T. K., World J Surg, 4(3): 271-7 (1980); Nicolai, J. P., et al., Aesthetic Plast Surg, 11(1):29-32 (1987). Clinical scar management involves consideration of both the continual physical assessment of the scar, including body location and the patient's previous scar history, with a clinical regimen that is often modulated over the course of treatment. Accepted conservative treatments for hypertrophic scars and keloids are limited to surgery, corticosteroid injections, radiotherapy, silicone gel sheeting and pressure therapy. See, e.g., Mustoe, T. A., et al., Plast Reconstr Surg, 110(2):560-71 (2002). While scar management has recently experienced new modalities for the physician, scar outcome is still largely unpredictable. Treatments that specifically target the biological mechanisms responsible for hypertrophic scars and keloids would complement existing therapy and could improve current scar outcome.
Cutaneous scarring is described as macroscopic disruptions of normal skin architecture and function, which arise as a consequence of wound repair and proceeds as a fibroproliferative response. See. e.g., Clark, R. A. F., Wound Repair: Overview and General Considerations, in THE MOLECULAR AND CELLULAR BIOLOGY OF WOUND REPAIR, (Ed., R. A. F. Clark), 1988, pp. 3-35. The pathogenetic and biological profile of keloids and hypertrophic scars is not fully understood. Keloids are hallmarked by growth beyond the margins of the original trauma site, are associated with familial disposition, and rarely regress. See, e.g., Tredget, E. E., Ann N Y Acad Sci, 888:165-82 (1999). Hypertrophic scars are raised, erythematous fibrous lesions which usually undergo resolution over time and are associated with contracture of tissue. See, e.g., Tredget, E. E., Ann N Y Acad Sci, 888:165-82 (1999). While keloids differ from hypertrophic scars in genetic linkage and immunological parameters, both are associated with fibroblast hyperproliferation and excessive extracellular matrix (ECM) deposition. See, e.g., Rockwell, W. B., et al., Plast Reconstr Surg, 84(5):827-37 (1989); Tsao, S. S., et al., Semin Cutan Med Surg, 21(1):46-75 (2002); Nemeth, A. J., J Dermatol Surg Oncol, 19(8):738-46 (1993).
Clearly, scarring remains a problem that is difficult to avoid in many situations. The present invention addresses this and other problems.